Matrix metaloproteinases activity during the evolution of hypoxic-ischemic brain damage in the immature rat. The effect of 1-methylnicotinamide (MNA).
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade the extracellular matrix and carry out key functions during brain development. Apart from a physiological role, excessive activation of MMPs in brain tissue has been postulated to represent a pathway for cell death arising from ischemia. To evaluate the possible involvement of MMPs in the perinatal brain asphyxia, we exposed 7-day-old rats to hypoxia-ischemia (HI). Unilateral HI was administered by ligation of the common carotid artery followed by hypoxia (7.4% O2/92.6% N2) for 65 minutes. This insult is known to produce brain damage confined to the cerebral hemisphere ipsilateral to the arterial occlusion in > 90% of animals. HI resulted in a significant elevation of MMP-2 and MMP-9 activity in the ipsilateral forebrain. The maximum activation was found at 48 hours and 7-14 days after the insult. These results suggest that early and late induction of MMPs may play a role in neuronal death as well as in repair processes. The treatment of animals subjected to HI with 1-methylnicotinamide (MNA), the anti-inflammatory agent, led to the inhibition of MMP-9 in an acute phase of ischemic damage and to the activation of MMP-2 in the later stages after injury. The timing of MMPs modulation by MNA may indicate its possible therapeutic implications.
Dragun
P
P
NeuroRepair Department, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Makarewicz
D
D
Wójcik
L
L
Ziemka-Nałecz
M
M
Słomka
M
M
Zalewska
T
T
D000375:Aging / Q000502:physiology; D000818:Animals; D000893:Anti-Inflammatory Agents; D001921:Brain / Q000201:enzymology / Q000254:growth & development / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D018722:Nicotinic Agonists; D009536:Niacinamide; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C024058:N(1)-methylnicotinamide